There have been mixed results regarding the relationship among short chain fatty acids (SCFAs), microbiota, and obesity in human studies. We selected studies that provided data on SCFA levels or fecal microbiota abundance in obese and nonobese individuals and then combined the published estimates using a random-effects meta-analysis. Obese individuals had significantly higher fecal concentrations of acetate (SMD (standardized mean differences) = 0.87, 95% CI (confidence interva) = 0.24–1.50, I2 (I–squared) = 88.5), propionate (SMD = 0.86, 95% CI = 0.35–1.36, I2 = 82.3%), and butyrate (SMD = 0.78, 95% CI = 0.29–1.27, I2 = 81.7%) than nonobese controls. The subgroup analyses showed no evidence of heterogeneity among obese individuals with a BMI >30 kg/m2 (I2 = 0.0%). At the phylum level, the abundance of fecal microbiota was reduced in obese compared to nonobese individuals, but the difference was not statistically significant (Bacteroidetes phylum, SMD = −0.36, 95% CI = −0.73–0.01; Firmicutes phylum, SMD = −0.10, 95% CI = −0.31–0.10). The currently available human case-control studies show that obesity is associated with high levels of SCFA but not gut microbiota richness at the phylum level. Additional well-designed studies with a considerable sample size are needed to clarify whether this association is causal, but it is also necessary to identify additional contributors to SCFA production, absorption, and excretion in humans.

Due to the continued high incidence and mortality rate worldwide, there is still a need to develop new strategies for the prevention, diagnosis and treatment of cardiovascular diseases (CVDs). Proper cardiovascular function depends on the coordinated interplay and communication between cardiomyocytes and noncardiomyocytes. Extracellular vesicles (EVs) are enclosed in a lipid bilayer and represent a significant mechanism for intracellular communication. By containing and transporting various bioactive molecules, such as micro-ribonucleic acids (miRs) and proteins, to target cells, EVs impart favourable, neutral or detrimental effects on recipient cells, such as modulating gene expression, influencing cell phenotype, affecting molecular pathways and mediating biological behaviours. EVs can be released by cardiovascular system-related cells, such as cardiomyocytes, endotheliocytes, fibroblasts, platelets, smooth muscle cells, leucocytes, monocytes and macrophages. EVs containing miRs and proteins regulate a multitude of diverse functions in target cells, maintaining cardiovascular balance and health or inducing pathological changes in CVDs. On the one hand, miRs and proteins transferred by EVs play biological roles in maintaining normal cardiac structure and function under physiological conditions. On the other hand, EVs change the composition of their miR and protein cargoes under pathological conditions, which gives rise to the development of CVDs. Therefore, EVs hold tremendous potential to prevent, diagnose and treat CVDs. The current article reviews the specific functions of EVs in different CVDs.

Background: The Pittsburgh Sleep Quality Index (PSQI) is a widely used self-report questionnaire that measures general sleep quality in general populations. However, its psychometric properties have yet to be thoroughly examined in longevous persons. Objectives: This study aimed to explore the reliability, validity and factor structure of the Chinese-language version of the PSQI in community-dwelling centenarians. Methods: A total of 958 centenarians (mean age = 102.8 years; 81.8% females) recruited from 18 regions in Hainan, China, completed the PSQI scale. Cronbach's alpha coefficient was used to measure the internal consistency. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed to explore the validity and factor structure of the PSQI in this sample. Correlations between the global PSQI score and physical function, depression symptoms, self-reported health status and subjective wellbeing were used to assess divergent validity. Results: The Cronbach's a coefficient of the PSQI was 0.68, and it increased to 0.78 after two components (medication use and daytime dysfunction) were removed. The Spearman correlation coefficients of the PSQI score with each component were statistically significant (P<0.01). EFA yielded a two-factor structure model of the original PSQI-7 and a one-factor structure model of the simplified PSQI-5. The one-factor model with five components (c 2 /df =1.59, CFI=0.99, RMSEA=0.03) fit the data well and had good configural invariance across demographic characteristics (0.53< D c 2 <5.58, P>0.05). Conclusions: The original PSQI showed acceptable applicability in Chinese communitydwelling centenarians, and its psychometric characteristics moderately improved after

To investigate the regulatory mechanism of miR-25 in sepsis-induced cardiomyocyte apoptosis. Rats models of sepsis were established by cecal ligation and puncture (CLP). Lipopolysaccharide (LPS)-induced cardiomyocyte was used as an in vitro model of sepsis. The expressions of miR-25, tensin homolog deleted on chromosome 10 (PTEN), Toll-like receptors 4 (TLR4), and p-p65 were analyzed by quantitative real-time PCR (qRT-PCR) and Western blot, respectively. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by ELISA. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated d-UTP nick end labeling (TUNEL) assay. The relationship between miR-25 and PTEN was measured by luciferase reporter assays. MiR-25 expression in serum of CLP rats and LPS-induced cardiomyocyte was decreased, while the contents of TNF-α and IL-6 were increased. Moreover, the expressions of PTEN, TLR4, and p-p65 in LPS-induced cardiomyocyte were significantly increased. Overexpression of miR-25 increased the survival rate of rats, inhibited LPS-increased cardiomyocyte apoptosis, reversed the increased expression of PTEN, TLR4, p-p65, TNF-α, and IL-6 induced by LPS. The luciferase assay demonstrated that PTEN was a target of miR-25. Additionally, pcDNA-PTEN reversed the inhibitory effect of miR-25 mimic on cardiomyocyte apoptosis, while TAK-242 (TLR-4 inhibitor) countered this effect. miR-25 reduced LPS-induced cardiomyocyte apoptosis by down-regulating PTEN/TLR4/NF-κB axis.

Aims: To investigate whether cryopreserved donor cornea could be used for therapeutic penetrating keratoplasty (PKP) to eradicate the infection, obviate complications, and preserve anatomical integrity in severe fungal keratitis. Methods: In this retrospective, consecutive case series, 45 eyes of 45 patients with severe fungal keratitis, which exhibited anterior chamber collapse, corneal perforation, and/or large suppurative corneal infiltrate, received therapeutic PKP after removal of the infected corneal tissue, irrigation of the anterior chamber by 0.2% fluconazole solution, iris dissection of fibrinoid membrane, and iridectomy and therapeutic PKP using corneas cryopreserved at −20°C. Results: Among 45 eyes, 39 eyes (86.7%) were successfully eradicated the fungal infection without recurrence and maintained their anatomical integrity without any complication. Four of 45 eyes (8.9%) showed postoperative rise of intraocular pressure, of which three were controlled with subsequent antiglaucoma surgeries, whereas one eye needed additional antiglaucoma medications. Two of 45 eyes (4.4%) were enucleated because of uncontrollable fungal infection and secondary retinal detachment, respectively. 23 eyes received subsequent optical PKP and, among them, 21 maintained clear corneal grafts and two suffered from graft failure due to allograft rejections. Conclusion: Cryopreserved donor corneas are effective substitutes in therapeutic PKP to control severe fungal corneal infection and preserve the global integrity, and may offer additional advantages over conventional PKP in reducing allograft rejection, eradicating fungal infection during the postoperative period, and improving the success of optical PKP for visual rehabilitation.

SummaryNatural killer (NK) cell adoptive transfer is a promising approach for cancer immunotherapy; however, its development has been hindered by the lack of efficient methods to produce large numbers of functional NK cells. In this study, we engineered the leukaemia cell line K562 to express CD137 ligand (CD137L) and membrane-bound interleukin (mbIL)-21 on the cell surface, and used these cells to expand NK cells from the peripheral blood mononuclear cells. We found that purity of the NK cells (CD3 -CD56 + /CD16 + ) increased from less than 30% to above 95% after a 3-week expansion and proliferation of the cells was sustained for more than 8 weeks. The surface expression of NK cell activating and inhibitory receptors, except for NKp80, was clearly increased with the expansion, and NK cell-mediated killing activity was also enhanced significantly. However, these changes in both phenotype and function were clearly reversed by JSI-124, a specific signal transducer and activator of transcription-3 (STAT-3) inhibitor. Taken together, data showed that the combination of mbIL-21 and CD137L could efficiently induce the formation of functional human NK cells from peripheral blood mononuclear cells, and STAT-3 inhibition could impair this induction. Therefore, STAT-3 activation may benefit human NK cell proliferation and cytotoxicity, and provide valuable clinical applications in NK cell immunotherapy against viral infectious diseases and cancers.

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Objectives: The oldest old population has become the fastest growing segment with excess need of care and social support, it is crucial to improve the health-related quality of life (HRQoL) of these populations. This study seeks to evaluate the health status and to investigate modifiable factors associated with health-related quality of life for oldest old adults in China. Design: A cross-sectional population-based study. Setting: Hainan Province in the south of China. Participants: 1,278 adults aged 80 years or older. Methods: HRQoL was assessed by three-level EuroQol-5D scale (EQ-5D-3L) and a visual analogue scale (VAS). Demographic and healthrelated variables were analysed by estimating mean values and standard deviations for continuous variables, percentages and standard deviations for categorical variables. Tobit regressions, ordinary least Squared (OLS) regressions and ordered probit regressions were adopted to determine the associated factors for overall HRQoL and for each health dimension. Results: Anxiety/depression was the least reported problem while mobility was the most frequently reported with problem. Female respondents had lower EQ-5D score (0.76 vs. 0.86) and VAS score (66.55 vs. 69.84) than male respondents. Better health-related quality of life was significantly associated with higher BMI, no drinking habit, more leisure activities, living with family members, good sleeping quality, closer social and family connections, fewer numbers of drugs consumed per day, without having hearing or visual impairment, and fewer chronic conditions, after controlling for potential confounders. Conclusion: Findings from this study suggested that quality of life was not only associated with age-related diseases, but also correlated with a range of health-related lifestyles, and factors indicating social and family support.